EU/3/03/182

Orphan designation

On 12 December 2003, orphan designation (EU/3/03/182) was granted by the European Commission to Axovan Europe Ltd., United Kingdom, for 5-methyl-pyridine-2-sulfonic acid 6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-1H-tetrazol-5-yl-pyridin-4-yl)-pyrimidin-4-ylamide sodium salt (1:2) (clazosentan) for the treatment of aneurysmal subarachnoid haemorrhage.

The sponsorship was transferred to Actelion Registration Limited, United Kingdom, in January 2005.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

A cerebral aneurysm refers to a blood vessel within the brain that weakens over time and undergoes widening. This usually occurs at the junctions of the large arteries at the base of the brain. As the blood vessel weakens, it begins to bulge out like a balloon. The larger the balloon becomes, the greater the risk it may burst, resulting in haemorrhage (bleeding) into the subarachnoid space (membranous space surrounding the brain) and ensuing spasm (uncontrollable tightening) of the brain blood vessels, leading to further oxygen shortage in the brain cells. This cascade of effects can ultimately impair the brain functions.

Aneurysms in the brain are considered to be acquired, in other words they are not present at birth but develop over a lifetime. However, evidence indicates that genetic factors make some people more likely to develop brain aneurysms.

At the time of designation, aneurysmal subarachnoid haemorrhage affected approximately 1.25 in 10,000 people in the European Union (EU). This was equivalent to a total of around 48,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union. At the time of designation, this represented a population of 382,800,000 (Eurostat 2003).

Further to surgical intervention, one medicinal product was authorised for the treatment of aneurysmal subarachnoid haemorrhage in the Community at the time of submission of the application for orphan drug designation.

Clazosentan might be of potential significant benefit for the treatment of aneurysmal subarachnoid haemorrhage. This is because it may prevent the complications that are resulting from insufficient blood supply to the brain. This benefit will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Clazosentan opposes the effect of a substance called endothelin. Endothelin, which is naturally produced by some type of cells of the body, can cause narrowing of blood vessels. Clazosentan blocks the effect of endothelin and the blood vessels can become wider.As such it could prevent and relieve spasm of the blood vessels.

At the time of submission of the application for orphan designation, clinical trials in patients with aneurysmal subarachnoid haemorrhage were ongoing.

Clazosentan was not marketed anywhere worldwide for the treatment of aneurysmal subarachnoid haemorrhage or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 November 2003 recommending the granting of this designation.

the existence or not of alternative methods of diagnosis, prevention or treatment and

either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.